Peptide Receptor Radionuclide Therapy (PRRT) with 177Lu-DOTATATE in Individuals with Neck or Mediastinal Paraganglioma (PGL)

Abstract

Paragangliomas (PGLs) are neuroendocrine tum-ors that arise embryologically from the neural crest. Sympathetic PGLs can be located in the thoracic-abdominal region while parasympathetic PGLs are mainly situated in the head and neck region. Most PGLs are sporadic, but in 30% of cases they are hereditary (associated with mutations of SDHB, SDHC, SDHD, SDHAF2, SDHA, TMEM, MAX, and VHL); they can be classified into 4 different paraganglioma syndromes: PGL1, PGL2, PGL3, and PGL4. Surgery is the treatment of choice for both sympathetic and parasympathetic PGLs. Other types of treatment include medical agents (such as gemcitabine, cisplatin, or sunitinib) and radiotherapy (external-beam radiotherapy or stereotactic surgery). Surgery and radiotherapy, however, can cause important side effects such as vascular complications and peripheral nerve damage (hypoglossal, recurrent laryngeal, glossopharyngeal, and vagus). Another possible treatment option is the use of peptide receptor radionuclide therapy (PRRT), including PRRT with 177Lu-DOTATATE. We studied 4 patients with hereditary nonmetastatic paraganglioma syndrome type 1 (PGL1), with progressive disease, in whom surgical excision was not possible. They were treated with 177Lu-DOTATATE (3-5 cycles) and all had a partial response (PR) or a stable disease (SD) to the treatment. In conclusion, a good alternative treatment when surgical or radiation therapy are contraindicated could be radiometabolic therapy with 177Lu-DOTATATE.

The management of head-and-neck paragangliomas

“…PRRT with radiolabelled agents (MIBG or SSA) is an option for the treatment of malignant or inoperable PGLs with high uptake for the specific radiopharmaceutical -up to half of the cases show symptomatic and partial tumour response (Mukherjee et al 2001, Van Essen et al 2006, Gonias et al 2009, Zovato et al 2012. No studies have evaluated the possible efficacy of PRRT in earlier stages, on a more limited malignant tumour load (perhaps on lower doses that might decrease the risk of severe toxic reactions).…”

The Challenges of Treating Paraganglioma Patients with 177Lu-DOTATATE PRRT: Catecholamine Crises, Tumor Lysis Syndrome and the Need for Modification of Treatment Protocols

“…Successful treatment has been described in a case of spinal and cranial paraganglioma [16], four patients with non-metastatic neck or mediastinal paragangioma [17], and a carotid body paraganglioma [18]. None of these studies described details of the 177 Lu-DOTATA TE therapy protocol used or any adverse reactions encountered.…”

Could 68Ga-somatostatin analogues replace other PET tracers in evaluating extra-adrenal paragangliomas?

“…Beyond the diagnostic accuracy, an undoubted advantage of somatostatin receptor PET compared to other PET tracers is the ability to select patients potentially eligible for peptide radioreceptor therapy, which a preliminary study has described as feasible for patients with extra-adrenal PGL representing a good alternative treatment when surgical or radiation therapy are contraindicated [20].…”